What's new?

Many patients diagnosed with esophageal adenocarcinoma (EAC) are in advanced stages of disease, greatly reducing their chances of survival. Since the absolute risk in the population is low, however, universal endoscopic screening is impractical, necessitating the development of novel preventive and early-detection strategies. Here, prediction models based on EAC risk factors were tested for their ability to identify individuals at increased risk of the disease. The most refined model successfully identified 94 percent of patients with EAC. Such prediction models could facilitate EAC prevention and detection.

What's new

Inhibitors of 5alpha-reductase enzyme (5-ARIs) are commonly used in the treatment of benign prostatic hyperplasia (BPH). But while clinical trials showed that 5-ARIs lower overall prostate cancer (PCa) risk compared to placebo, they reported a higher proportion of high-grade tumors among long-term users. Here, the authors evaluated PCa-specific survival for 5-ARIs users and non-users among men diagnosed with prostate cancer. The previously reported elevated risk of high-grade PCa among 5-ARIs users does not affect the risk of PCa death, at least in the short-term. Alpha-blockers, also commonly used in BPH management, appear indicative of an impaired prognosis in PCa patients.

What's new?

The “cure proportion” for a particular type of cancer indicates how many patients will avoid relapse. This aids researchers and physicians in estimating survival outcomes in the general population. In this study, the authors analyzed the cure proportion for patients with Stage III and IV cutaneous malignant melanoma (CMM) in Sweden. They found that patients with non-ulcerated Stage III CMM had a significantly higher cure proportion than patients with ulcerated Stage III CMM or Stage IV disease. These results indicate that further analysis of biologic differences between ulcerated and non-ulcerated tumors is needed.

What's new?

Gastric cancer incidence varies greatly worldwide, but is consistently twice as high in men as in women. Hormone-related factors are hypothesized to be associated with lower risk of gastric cancer in women, but these factors have not been fully explored in populations with a high background risk of gastric cancer. Based on statistical analyses among a prospective cohort study of Chinese in Singapore, here the authors found that reproductive factors associated with a longer window of fertility and the use of exogenous hormones reduce gastric cancer development in a cohort of women with a high background risk of gastric cancer.

What's new?

While dietary lycopene and tomato products have been inversely associated with prostate cancer incidence, there is limited evidence for an association between their consumption and prostate-cancer specific mortality (PCSM). This is the first study to comprehensively examine the associations of pre- and post-diagnosis lycopene and tomato product intake with PCSM among men with nonmetastatic prostate cancer. No association was observed between pre- or post-diagnosis intake and PCSM using a single dietary measurement. However, consistently high intake of lycopene after diagnosis assessed using repeated dietary questionnaires was associated with significantly lower risk of PCSM among men diagnosed with high-risk prostate cancer.

What's new?

Socioeconomic status (SES) is a significant factor in access to health care but its influence on cancer survival in high-income countries with mandatory health insurance is unclear. Here the authors investigate the influence of SES on childhood cancer survival in Switzerland. They report a striking socioeconomic gap in survival of pediatric CNS tumor, but not leukemia, patients. This result points to a lack of therapy standardization in the treatment of pediatric CNS tumors, underscoring the need for universal access to optimal cancer treatment for all patients even in an affluent country like Switzerland.

What's new?

How well does quadrivalent HPV vaccination protect girls from cancer? These authors followed the entire population of Swedish girls ages 13–29 for high-grade cervical lesions and quadrivalent HPV vaccination through a registry-based study. Those receiving the quadrivalent HPV vaccine were less likely to develop of CIN2 and CIN3. In Sweden, the organized cervical screening program begins at age 23. This study showed that the vaccine was more effective against CIN2 and CIN3 if given before age 17 years. Longer follow-up of vaccinated women is needed to determine the long-term effectiveness of Sweden's vaccination program against invasive cervical cancer.

What's new?

High doses of radiation can increase cancer risk. However, less is known about the effects of chronic, long-term exposure to low doses of radiation, such as that experienced by X-ray technicians. In this study, the authors estimated the total radiation dose received by more than 27,000 Chinese medical workers, over a period of 30 years. They found that the risk for solid cancers increased significantly as cumulative radiation exposure increased. These results have important implications for the development of radiation-safety precautions.

What's new?

Methylation patterns hold clues to the risk of disease progression in men with prostate cancer. Whether risk of malignant transformation from benign prostatic disease can be similarly deduced is unknown. Here, methylation patterns in gene promoter regions were analyzed in benign tissue samples collected from men who later developed prostate cancer. In white men only, methylation of a known tumor suppressor gene in premalignant benign prostate was associated with an increased risk for subsequent disease progression. The results suggest that race-specific methylation panels could play a role in the early detection of aggressive prostate cancer.

What's new?

Circulating tumor cells (CTCs) carry vital information about a tumor but are few in number, challenging their use as diagnostic tools. Moreover, not all CTCs express epithelial markers, holding back the advance of promising approaches based on the combination of cell-surface antigen targeting with microfluidic technology. Here, an antigen-independent microfluidic separation platform based on differences in cell size and deformability is shown to effectively capture CTCs, enabling the isolation of CTCs from tumors lacking epithelial markers. The capture of viable CTCs from peripheral blood paves the way to the future use of “liquid biopsies” in cancer diagnosis.

What's new?

Chromothripsis is characterized by extensive locally clustered genomic rearrangements, whereby chromosome shattering is followed by rejoining of the DNA fragments by error-prone repair mechanisms. The present study elaborates on a previously proposed role in the initiation of chromothripsis for telomere erosion and breakage-fusion-bridge (BFB) cycles, in which chromosomes repeatedly break and are rejoined. In cells lacking normal mechanisms for genome preservation, telomere attrition and BFB cycles induced chromothripsis. Subsequent activation of tumor-specific telomere maintenance mechanisms prevented further chromosomal shattering. The findings suggest that telomere maintenance pathways may represent therapeutic targets in chromothripsis-positive tumors.

What's new?

Certain parasites may do more than cause chronic health problems. They may also lead to cancer. Some of these infections, such as “snail fever” (schistosomiasis), are already known to be linked to cancer. In this study, however, the authors identified six additional parasitic infections that may also increase risk. The carcinogenic mechanisms triggered by these infections include chronic inflammation, DNA damage, altered gene expression and immune evasion. Because billions of people are infected with various parasites worldwide, these findings raise serious public health concerns, and further research is urgently needed.

What's new?

Cervical cancer screening increasingly is based on the detection of high-risk human papillomavirus (hrHPV), including types 16 and 18, the prevalence of which is declining in areas with HPV vaccination. Almost nothing is known, however, about how HPV vaccination could impact cervical screening. Drawing on samples in the Scottish HPV Archive, the authors of the present study show that HPV 16 and/or 18 infection is significantly reduced among vaccinated women. Similar reductions were not observed for non-16/18 hrHPV. Moreover, the proportion of non-16/18 hrHPV associated with low-grade cervical abnormalities was increased in vaccinated women, potentially affecting HPV assay performance.

What's new?

Human papillomavirus (HPV) testing has a high negative predictive value for detecting histological cervical intraepithelial neoplasia (CIN). False-negative HPV results can occur, however, though their clinical relevance is little understood. Using data from the U.S.-based ATHENA study, the authors of the present report show that only a very small percentage of CIN grade 3/adenocarcinoma in situ (ACIS) lesions were missed by the cobas HPV Test, which identifies 14 high-risk HPV types. False-negatives by cobas testing were compared with Linear Array and Amplicor testing. Most missed CIN3/ACIS cases were associated with HPV types not included in current tests.

What's new?

What drives esophageal cancer? These authors combed through cDNA microarrays and found that esophageal squamous cell carcinoma contains lower level of the tumor suppressor DESC1. They then investigated the molecular activity of the DESC1 protein. Under favorable conditions, the cells grew normally, but the presence of DESC1 sensitized cells to conditions that induce apoptosis. That is, the cells without DESC1 withstood the apoptotic stresses, while those expressing DESC1 perished. The location of DESC1 in the cell membrane allows it to interact with the extracellular environment, and they showed that it thus hinders cell colony formation.

What's new?

In many cancers, the types and ratios of T cells and B cells within a tumor correlate with prognosis. They may also affect potential immunotherapies. Some tumor-infiltrating lymphocytes (TILs) can suppress the anti-tumor response, while others enhance it. In this study, the authors extensively analyzed TILs in oral squamous cell carcinoma (OSCC) tumors. They found evidence of a tumor-specific immune response among both the T and B cells within these tumors. These results may help researchers develop immune-related therapies for oral cancers.

What's new?

A small percentage of healthy blood donors carry IgM antibodies that react with carbohydrate antigens, including tumor-associated gangliosides GD2 and GD3. Ganglioside-targeting IgM can kill via complement activation, however, remains unclear. In this study, donor IgM antibodies effectively killed human neuroblastoma Kelly cells and certain melanoma cells in vitro, using distinct gangliosides as targets for cytotoxic attack. Complement attack was countered, however, by membrane complement regulator proteins (mCRPs), which are highly expressed on most melanoma cells. Despite neutralization with anti-mCRP antibodies, some melanoma cells maintained resistance, suggesting that humoral anti-melanoma activity is prevented through other mechanisms.

What's new?

Patients whose gastric cancer returns despite curative surgery tend to suffer poor prognosis. According to the authors of this study; however, it may be possible to catch recurrent disease before it reaches advanced stages using circulating plasma (cp) DNA, a blood-based biomarker. In advanced gastric cancer patients, cpDNA levels were associated with tumor recurrence and initial recurrence pattern, with high cpDNA levels signaling an increased likelihood of peritoneal recurrence versus locoregional or distant recurrence. Primary tumor mutations in cpDNA were linked to reductions in 5-year survival, suggesting that cpDNA mutational status can predict poor prognosis in late-stage disease.

What's new?

New biomarkers for the early detection of ovarian cancer (OC) are urgently needed. In this blinded, prospective study, the authors identified Protein Z as a novel early marker for Type I and Type II OC that can also discriminate between the two types. When Protein Z levels were combined with CA-125, results for early detection were even better. They may also enhance the Risk of Ovarian Cancer algorithm. These findings should help researchers develop more sensitive and specific screening panels for early-stage OC.

What's new?

Oxaliplatin frequently is used in combination with 5-fluorouracil and leucovorin as a first-line therapy against colorectal cancer (CRC). However, the efficacy of oxaliplatin differs greatly between patients. Oxaliplatin availability to cells and its subsequent detoxification depend on the activity of certain metabolic and transporter enzymes, some of which, according to this study, carry genetic variants that alter the drug's effectiveness. The authors show that interactions between oxaliplatin and single nucleotide polymorphisms (SNPs) in multiple transporter and metabolism genes are associated with overall CRC survival. The SNPs could be used to predict the likelihood of response to oxaliplatin.

What's new?

Sunitinib, a first-line therapy for advanced renal cell carcinoma, produces durable responses in patients. Nonetheless, as with other receptor tyrosine kinase inhibitors (TKIs), tumors inevitably become resistant to the drug. Here, phosphoproteomic profiling reveals that sunitinib not only reduces the phosphorylation of numerous proteins, consistent with TKI activity, but also enhances the phosphorylation of other proteins, including the pro-survival players FAK and Axl. Combination treatment with an Axl inhibitor potentiated the antitumor activity of sunitinib. The findings shed light on the pharmacodynamic effects of sunitinib and provide insight into leads for overcoming resistance.

What's new?

Thanks to a new strategy of topical vasoconstrictor application, it may be possible to suppress oral mucositis and alopecia, potentially severe side effects of chemotherapy. However, whether topical vasoconstriction, which limits skin and mucosal exposure to cancer therapy, also provides a sanctuary for potentially relapsing tumor cells is unknown. Here, no detectable sanctuary of L1210 leukemia cells was formed in mice treated with orotopical or topical vasoconstrictor before systemic cyclophosphamide was administered, even at topical vasoconstrictor doses well above those imagined for clinical use. The strategy is being investigated further in a newly opened Phase I/IIa trial.